Examples of substances conventionally used as chemotherapeutic agents for cancer include alkylating agents such as cyclophosphamide, antimetabolites such as methotrexate and fluorouracil, antibiotics such as adriamycin, mitomycin and bleomycin, plant-derived agents such as paclitaxel, vincristine and etoposide and metal complexes such as a platinum formulation. None of them, however, have satisfactory anti-tumor effect and thus there has been a strong need for development of a novel anti-tumor agent.
Formulations comprising an anti-tumor platinum complex as an active element are known as platinum formulations. Examples of such anti-tumor platinum complexes include cisplatin, carboplatin, nedaplatin, zeniplatin, enloplatin, lobaplatin, ormaplatin, loboplatin, sebriplatin, oxaliplatin, miboplatin and spiroplatin. Such platinum formulations have been approved and developed for application to testicular tumor, bladder cancer, renal pelvic/ureteral tumor, prostate cancer, ovarian cancer, head and neck cancer, non-small-cell lung cancer, esophageal cancer, cervical cancer, neuroblastoma, gastric cancer, osteosarcoma, small cell lung cancer, malignant lymphoma, hepatocellular carcinoma or the like. In addition, combination therapy for various cancers has also been approved or developed by combining a platinum formulation including an anti-tumor platinum complex with various drugs, for example, with paclitaxel for non-small-cell lung cancer and with gemcitabine for non-small-cell lung cancer.
In a test by Abratt et al., a median survival period obtained with combined use of vinorelbine and carboplatin was 8.6 months while a median survival period obtained with combined use of vinorelbine and gemcitabine was 11.5 months. These results showed that combination therapy without a platinum formulation was better than combination therapy with a platinum formulation. That is to say that even if a platinum formulation has anti-tumor effect, the effect is not necessarily enhanced by simply combining with other drugs, and that selection of drugs for anti-tumor effect enhancement is yet unobvious (Non-patent references 1-9)
Furthermore, 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide is known as a VEGF receptor kinase inhibitory substance (Patent References 1-2).
However, there is no report as to whether or not pharmaceutical compositions comprising these substances in combination have any anti-tumor effect.
[Patent Reference 1] International Publication No. WO2002/32872
[Patent Reference 2] International Publication No. WO2005/063713
[Non-Patent Reference 1] Paclitaxel+carboplatin: Paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a phase II trial (J. Clin Oncol., 14(7), 2054-2060, 1996)
[Non-Patent Reference 2] Paclitaxel+cisplatin: Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. (J. Clin Oncol., 18(19), 3390-3399, 2000)
[Non-Patent Reference 3] Vinorelbine+cisplatin: Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. (J. Clin Oncol., 16(7), 2459-65, 1998)
[Non-Patent Reference 4] Gemcitabine+cisplatin: Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. (J. Clin Oncol., 18(1)), 122-130, 2000)
[Non-Patent Reference 5] Gemcitabine+carboplatin: Phase II study of gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer. (Cancer Chemother Pharmacol., 60 (4), 601-607, 2007)
[Non-Patent Reference 6] CPT-11 (Irinotecan)+cisplatin: A phase II study of irinotecan plus cisplatin for patients with advanced stage IIIB or IV NSCLC previously treated with nonplatinum-based chemotherapy. (Cancer, 107(4), 799-805, 2006) [Non-Patent Reference 7] J. Clin Oncol. 24(3):419-430, 2006
[Non-Patent Reference 8] Other: Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. (Ann Oncol., 18(2), 317-323, 2006) [Non-Patent Reference 9] Lung Cancer 2005, Vol. 49, No2, pp. 233-240